Korean J Anat.  2006 Oct;39(5):401-406.

HO-1 Mediates Intracellular Calcium Modulation and Inhibits TNF-alpha-induced NF-kappaB Activity in Human Colonic Epithelial Cell Line

• Kim YR
• Jang SJ

Abstract

Heme oxygenage-1 (HO-1) is the rate-limiting enzyme in heme catabolism, which leads to the generation of carbon monoxide (CO), biliverdin, and free iron. HO-1 has been known to show strong immunosuppressive properties although its mechanisms are not completely understood. In this study, it was therefore investigated anti-inflammatory properties of HO-1 in HT-29 cell, human colonic epithelial cell line. CoPPIX, HO-1 inducer, induced HO-1 expression without NF-kappa B activation and significantly blocked the I kappa B-alpha degradation by TNF-alpha in HT-29. Inhibition of HO-1 activity by ZnPPIX reversed the suppressive effects of CoPPIX on I kappa B-alpha degradation by TNF-alpha. Calcium chelating agent BAPTA/AM and calcium channel blockers, Verapamil and Flunarizine suppressed I kappa B-alpha degradation by TNF-alpha in HT-29 cells like CoPPIX while calcium ionophore A23187 also dose-dependently reversed the suppressive effects of CoPPIX on I kappa B-alpha degradation by TNF-alpha like a ZnPPIX. Interestingly, treatment of ZnPPIX increased basal intracellular calcium in HT-29 cells. Collectively, these results suggest that HO-1 exerts anti-inflammatory effects by down-regulation of NF-kappa B activity via suppression of intracellular calcium during pathogenesis of colitis in colonic epithelium.

Keyword

HO-1; NF-kappa B; Intracellular calcium; HT-29

MeSH Terms

Biliverdine
Calcimycin
Calcium Channel Blockers
Calcium*
Carbon Monoxide
Colitis
Colon*
Down-Regulation
Epithelial Cells*
Epithelium
Flunarizine
Heme
HT29 Cells
Humans*
Iron
Metabolism
NF-kappa B*
Tumor Necrosis Factor-alpha
Verapamil
Biliverdine
Calcimycin
Calcium
Calcium Channel Blockers
Carbon Monoxide
Flunarizine
Heme
Iron
NF-kappa B
Tumor Necrosis Factor-alpha
Verapamil